Hematological examination

This is a method by which abnormalities of the cells of the blood and their precursors in the bone marrow are investigated to diagnose the different kinds of anemia & leukemia.

Osteogenesis Imperfecta (OI) (Brittle bone diseases) 

It is a group of hereditary disorders caused by gene mutations that eventuate in defective synthesis of and thus premature degradation of type I collagen. The fundamental abnormality in all forms of OI is too little bone, resulting in extreme susceptibility to fractures. The bones show marked cortical thinning and attenuation of trabeculae. 

Extraskeletal manifestations also occur because type I collagen is a major component of extracellular matrix in other parts of the body. The classic finding of blue sclerae  is attributable to decreased scleral collagen content; this causes a relative transparency that allows the underlying choroid to be seen. Hearing loss can be related to conduction defects in the middle and inner ear bones, and small misshapen teeth are a result of dentin deficiency 

THYROIDITIS 
The more common and clinically significant thyroidites are:  
1. Hashimoto thyroiditis 
2. Subacute granulomatous thyroiditis
3. Subacute lymphocytic thyroiditis 

Hashimoto thyroiditis 

Hashimoto thyroiditis (Chronic Lymphocytic Thyroiditis) is the most common cause of hypothyroidism. It results from gradual autoimmune destruction of the thyroid gland. There is striking female predominance (10: 1 to 20:1), and is most prevalent around a mean age of 50 years. 

Pathogenesis 
• The dominant feature is progressive destruction of thyroid follicular epithelial cells with gradual replacement by mononuclear cell infiltration and fibrosis. 
• Sensitization of CD4+ T-helper cells to thyroid antigens seems to be the initiating event.
• The reaction of CD4+ T cells with thyroid antigens produces interferon γ  which promote inflammation and activate macrophages. Injury to the thyroid results from the toxic products of these inflammatory cells. 
• CD8+ cytotoxic T cells also contribute to epithelial cells killing as are natural killer cells. 
• There is a significant genetic component to disease pathogenesis. This is supported by 
1.  The increased frequency of the disease in first-degree relatives, 
2.  Unaffected family members often have circulating thyroid autoantibodies.  

Gross features 
• The thyroid shows moderate, diffuse, and symmetric enlargement.
• The cut surface is pale, gray-tan, firm, nodular and somewhat friable. 
• Eventually there is thyroid atrophy 

Microscopic features

• There is widespread, diffuse infiltration of the parenchyma by small lymphocytes, plasma cells.  The lymphocytes are also form follicles some with well-developed germinal centers 
• The thyroid follicles are atrophic and lined by epithelial cells having abundant eosinophilic, granular cytoplasm (Hurthle cells). This is a metaplastic response to the ongoing injury; ultrastructurally the Hurthle cells are stuffed by numerous mitochondria. 
• Interstitial connective tissue is increased and may be abundant.

Hashimoto thyroiditis presents as painless symmetrical goiter, usually with some degree of hypothyroidism. In some cases there is an initial transient thyrotoxicosis caused by disruption of thyroid follicles, with secondary release of thyroid hormones ("hashitoxicosis"). As hypothyroidism supervenes T4 and T3 levels progressively fall & TSH levels are increased. Patients often have other autoimmune diseases and are at increased risk for the development of B-cell non-Hodgkin lymphomas. 

Subacute Granulomatous (de Quervain) Thyroiditis 

Subacute Granulomatous (de Quervain) Thyroiditis is much less common than Hashimoto disease.

- It is most common around the age of 40 years and occurs more frequently in women than in men.

- An upper respiratory infection just before the onset of thyroiditis. Thus, a viral infection is probably the cause.

- There is firm uni- or bilateral enlargement of the gland.

Microscopically, there is disruption of thyroid follicles, with extravasation of colloid. The extravasated colloid provokes a granulomatous reaction, with giant cells.
Thyroid function tests are those of thyrotoxicosis but with progression and gland destruction, a transient hypothyroid phase occurs. The condition is self-limited, with most patients returning to a euthyroid state within at most 2 months.

Subacute Lymphocytic Thyroiditis

Subacute Lymphocytic Thyroiditis may follow pregnancy (postpartum thyroiditis).

- It is most likely autoimmune in etiology, because circulating antithyroid antibodies are found in the majority of patients.

- It mostly affects middle-aged women and present as painless, mild, symmetric neck mass. Initially, there is thyrotoxicosis, followed by return to a euthyroid state within a few months. In a minority there is progression to hypothyroidism.

Microscopically, there is a lymphocytic infiltration and hyperplastic germinal center within the thyroid parenchyma; unlike Hashimoto thyroiditis, follicular atrophy or Hürthle cell metaplasia are not commonly seen.

Riedel thyroiditis 

Riedel thyroiditis is a rare disorder of unknown etiology, characterized by extensive fibrosis involving the thyroid and the surrounding neck structures. The presence of a hard and fixed thyroid mass may be confused clinically with thyroid cancer. It may be associated with idiopathic fibrosis in other sites, such as the retroperitoneum. The presence of circulating antithyroid antibodies in most patients suggests an autoimmune etiology. 

Actinic keratosis
1. Dry, scaly plaques with an erythematous base.
2. Similar to actinic cheilosis, which occurs along the vermilion border of the lower lip.
3. Caused by sun damage to the skin.
4. Dysplastic lesion, may be premalignant.

VIRAL DISEASES

RABIES (Hydrophobia)

An acute infectious disease of mammals, especially carnivores, characterized by CNS pathology leading to paralysis and death.

Etiology and Epidemiology

Rabies is caused by a neurotropic virus often present in the saliva of rabid animals

Pathology

The virus travels from the site of entry via peripheral nerves to the spinal cord and the brain, where it multiplies; it continues through efferent nerves to the salivary glands and into the saliva.

microscopic examination shows perivascular collections of lymphocytes but little destruction of nerve cells. Intracytoplasmic inclusion bodies (Negri bodies), usually in the cornu Ammonis, are pathognomonic of rabies, but these bodies are not always found.

Sign/Symptoms

In humans, the incubation period varies from 10 days to > 1 yr and averages 30 to 50 days.

Rabies commonly begins with a short period of depression, restlessness, malaise, and fever. Restlessness increases to uncontrollable excitement, with excessive salivation and excruciatingly painful spasms of the laryngeal and pharyngeal muscles. The spasms, which result from reflex irritability of the deglutition and respiration centers, are easily precipitated Hysteria due to fright

Prognosis and Treatment

Death from asphyxia, exhaustion, or general paralysis usually occurs within 3 to 10 days after onset of symptoms

Muscle pathology
1. Myasthenia gravis
a. An autoimmune disease caused by autoantibodies to acetylcholine receptors at the neuromuscular junctions.
b. Characterized by muscle weakness or the inability to maintain long durations of muscle contractions; this worsens during exercise but recovers after rest.
c. Affects various muscle groups, including:
(1) Eyes—diplopia, ptosis.
(2) Neck—dysphagia, problems swallowing or speaking.
(3) Extremities—arms and legs.
d. Treatment: cholinesterase inhibitors(neostigmine), anti-immune therapy.

2. Muscle tumors
a. Rhabdomyoma—benign tumor of skeletal muscle.
b. Leiomyoma
(1) Benign tumor of smooth muscle.
(2) Most common tumor found in women.
(3) Usually affects the uterus, although it can occur anywhere.
c. Rhabdomyosarcoma
(1) Malignant tumor of skeletal muscle.
(2) Most common sarcoma found in children.
(3) Usually affects head and neck region—orbit, nasal cavity, and nasopharynx.